This is a Study to Determine the Antidepressant Effects of AZD6765

• AZD6765 (Drug): Single IV infusion of 150 mg AZD6765.
• Placebo to AZD6765 (Drug): Single IV infusion of Placebo to AZD6765

Primary outcomes

• Montgomery-Asberg Depression Rating Scale (MADRS) Total Score. [60 minutes (min) prior to dosing (baseline); and 60 min, 80 min, 110 min, 230 min, 1 day, 2 days, 3 days and 7 days following dosing.]: Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item instrument used for the evaluation of depressive symptoms. Each item is rated on a scale of 0 to 6 (with higher scores indicating more severe depression). The individual item scores are added together to form a total score, ranging between 0 and 60. 0 is considered the best score, 60 the worst.

Secondary outcomes

• The Number of Participants With Montgomery-Asberg Depression Rating Scale (MADRS) Total Score Less Than 10 (MADRS Remission). [60 minutes (min) prior to dosing (baseline); and 60 min, 80 min, 110 min, 230 min, 1 day, 2 days, 3 days and 7 days following dosing.]: Remission defined as a Montgomery-Asberg Depression Rating Scale (MADRS) total score <10. MADRS is a 10-item instrument used for the evaluation of depressive symptoms. Each item is rated on a scale of 0 to 6 (with higher scores indicating more severe depression). The individual item scores are added together to form a total score, ranging between 0 and 60. 0 is considered the best score, 60 the worst.
• The Number of Participants With at Least 50% Reduction in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (MADRS Response). [60 minutes (min) prior to dosing (baseline); and 60 min, 80 min, 110 min, 230 min, 1 day, 2 days, 3 days and 7 days following dosing.]: Response defined as a >= 50% reduction from baseline in MADRS total score. MADRS is a 10-item instrument used for the evaluation of depressive symptoms. Each item is rated on a scale of 0 to 6 (with higher scores indicating more severe depression). The individual item scores are added together to form a total score, ranging between 0 and 60. 0 is considered the best score, 60 the worst.
• Scale for Suicide Ideation (SSI) Total Score. [60 minutes (min) prior to dosing (baseline); and 60 min, 80 min, 110 min, 230 min, 1 day, 2 days, 3 days and 7 days following dosing.]: Scale for Suicide Ideation (SSI) is a 19-item scale designed to quantify the intensity of current conscious suicide ideation. Each item is rated on a scale of 0 to 2 (with higher scores indicating greater suicidal ideation). The individual item scores are added together to form a total score, ranging between 0 and 38. 0 is considered the best outcome, 38 the worst.
• Hamilton Anxiety Rating Scale (HAM-A) Total Score. [60 minutes (min) prior to dosing (baseline); and 230 min, 1 day, 2 days, 3 days and 7 days following dosing.]: Hamilton Anxiety Rating Scale (HAM-A) is used as a rating measure of anxiety severity. The scale consists of 14 items. Each item is rated on a scale of 0 to 4. The HAM-A total score is the sum of the 14 items and the score ranges from 0 to 56. 0 is considered the best outcome, 56 the worst.
• Hamilton Depression Rating Scale-17 Item (HDRS) Total Score [60 minutes (min) prior to dosing (baseline); and 60 min, 80 min, 110 min, 230 min, 1 day, 2 days, 3 days and 7 days following dosing]: Hamilton Depression Rating Scale-17 item (HDRS) is a scale that assesses depressive symptoms. HDRS consists of 17 symptoms, each of which is rated from 0 to 2 or 0 to 4, where 0 is none/absent. The total score is calculated as the sum of the 17 individual symptom scores; the total score can range from 0 to 52. Higher scores indicate more severe depression.
• Visual Analogue Scale (VAS) Depressed Score [60 minutes (min) prior to dosing (baseline); and 60 min, 80 min, 110 min, 230 min, 1 day, 2 days, 3 days and 7 days following dosing]: The Visual Analog Scale (VAS) Depressed is a 0 to 100-mm self-administered scale where patients rate their mood between "extreme sad" (0-mm) and "extreme happy" (100-mm), with a median "normal" point.
• Clinician-Administered Dissociative States Scale (CADSS) Score. [60 minutes (min) prior to dosing (baseline); and 60 min, 80 min, 110 min, 230 min, 1 day, 2 days, 3 days and 7 days following dosing]: Clinician- Administered Dissociative States Scale (CADSS) is a clinician-administered measure of perceptual, behavioral, and attentional alterations occurring during dissociative experiences. This scale involves a 23 questions and each is rated from 0 (not at all) to 4 (extremely). The total score is sum of the 23 items and range from 0 to 92 - best is 0 and worst is 92.
• Brief Psychiatric Rating Scale (BPRS) Score. [60 minutes (min) prior to dosing (baseline); and 60 min, 80 min, 110 min, 230 min, 1 day, 2 days, 3 days and 7 days following dosing.]: The Brief Psychiatric Rating Scale (BPRS) is a 18-item scale which measures symptoms and behaviors that are characteristic of schizophrenia. Each item is rated from 1 to 7 with higher score indicating greater severity. The total score is the sum of the 18 items, resulting in a range of scores from 18-126. 18 is considered to be the best outcome, 126 the worst.
• Beck Depression Inventory (BDI) Score. [60 minutes (min) prior to dosing (baseline); and 60 min, 80 min, 110 min, 230 min, 1 day, 2 days, 3 days and 7 days following dosing.]: Beck Depression Inventory (BDI) is a 21-question instrument for measuring the severity of depression. Each question has a set of at least four possible answer choices, ranging in intensity. A value of 0 to 3 is assigned for each answer and the total score is computed. Higher total scores indicate more severe depressive symptoms.
• Young Mania Rating Scale (YMRS) Score. [60 minutes (min) prior to dosing (baseline); and 60 min, 80 min, 110 min, 230 min, 1 day, 2 days, 3 days and 7 days following dosing.]: Young Mania Rating Scale (YMRS) consists of 11 items, rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe) or from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60. 0 is considered to be the best outcome, 60 the worst.
• Visual Analogue Scale (VAS) Anxious Score. [60 minutes (min) prior to dosing (baseline); and 60 min, 80 min, 110 min, 230 min, 1 day, 2 days, 3 days and 7 days following dosing.]: The Visual Analog Scale (VAS) Anxious is a 0 to 100-mm self-administered scale where patients rate their mood between "extreme sad" (0-mm) and "extreme happy" (100-mm), with a median "normal" point.
• Brief Psychiatric Rating Scale (BPRS) Positive Score. [60 minutes (min) prior to dosing (baseline); and 60 min, 80 min, 110 min, 230 min, 1 day, 2 days, 3 days and 7 days following dosing.]: Brief Psychiatric Rating Scale (BPRS) Positive is a 4-item scale which measures positive symptoms of schizophrenia (conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content). Each item is rated from 1 to 7 with higher score indicating greater severity. The total score is the sum of the 4 items, resulting in a range of scores from 4-28.

Sex: All, ages: 18 Years to 65 Years

Inclusion Criteria:

* Patients with a diagnosis of Major Depressive Disorder, currently depressed without psychotic features
* Females must be of non-childbearing potential.

Exclusion Criteria:

* Treatment with Clozapine or ECT within 3 months prior to study
* Current or past history of psychotic features or a diagnosis of schizophrenia or any other psychotic disorder as defined in the DSM-IV

Participant flow

Outcome results

• Montgomery-Asberg Depression Rating Scale (MADRS) Total Score. (Primary), Least squares mean, Units on a scale: AZD6765 (150 mg) 26.881 +/- 1.262; Placebo 28.618 +/- 1.314
• The Number of Participants With Montgomery-Asberg Depression Rating Scale (MADRS) Total Score Less Than 10 (MADRS Remission). (Secondary), Number, Participants: AZD6765 (150 mg) 2; Placebo 1
• The Number of Participants With at Least 50% Reduction in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (MADRS Response). (Secondary), Number, Participants: AZD6765 (150 mg) 5; Placebo 3
• Scale for Suicide Ideation (SSI) Total Score. (Secondary), Least squares mean, Units on a scale: AZD6765 (150 mg) 0.955 +/- 0.326; Placebo 0.939 +/- 0.330
• Hamilton Anxiety Rating Scale (HAM-A) Total Score. (Secondary), Least squares mean, Units on a scale: AZD6765 (150 mg) 16.211 +/- 1.181; Placebo 17.160 +/- 1.207
• Hamilton Depression Rating Scale-17 Item (HDRS) Total Score (Secondary), Least squares mean, Units on a scale: AZD6765 (150 mg) 15.930 +/- 0.977; Placebo 17.389 +/- 1.008
• Visual Analogue Scale (VAS) Depressed Score (Secondary), Least squares mean, Scores on a scale: AZD6765 (150 mg) 55.614 +/- 6.137; Placebo 60.562 +/- 6.197
• Clinician-Administered Dissociative States Scale (CADSS) Score. (Secondary), Least squares mean, Units on a scale: AZD6765 (150 mg) 4.104 +/- 0.900; Placebo 1.997 +/- 0.921
• Brief Psychiatric Rating Scale (BPRS) Score. (Secondary), Least squares mean, Units on a scale: AZD6765 (150 mg) 32.191 +/- 1.271; Placebo 32.896 +/- 1.314
• Beck Depression Inventory (BDI) Score. (Secondary), Least squares mean, Units on a scale: AZD6765 (150 mg) 21.081 +/- 2.524; Placebo 22.886 +/- 2.538
• Young Mania Rating Scale (YMRS) Score. (Secondary), Least squares mean, Units on a scale: AZD6765 (150 mg) 4.294 +/- 0.412; Placebo 3.626 +/- 0.427
• Visual Analogue Scale (VAS) Anxious Score. (Secondary), Least squares mean, Units on a scale: AZD6765 (150 mg) 43.898 +/- 7.415; Placebo 41.929 +/- 7.479
• Brief Psychiatric Rating Scale (BPRS) Positive Score. (Secondary), Least squares mean, Units on a scale: AZD6765 (150 mg) 9.433 +/- 0.264; Placebo 8.946 +/- 0.274

Adverse events

Other adverse events by term

17 more terms not shown.

• Results publication: Dean RL, Hurducas C, Hawton K, Spyridi S, Cowen PJ, Hollingsworth S, Marquardt T, Barnes A, Smith R, McShane R, Turner EH, Cipriani A. Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder. Cochrane Database Syst Rev. 2021 Sep 12;9(9):CD011612. doi: 10.1002/14651858.CD011612.pub3. PMID 34510411
• Results publication: Lepow L, Luckenbaugh DA, Park L, Henter ID, Zarate CA Jr. Case series: Antidepressant effects of low-affinity and low-trapping NMDA receptor antagonists did not predict response to ketamine in seven subjects. J Psychiatr Res. 2017 Mar;86:55-57. doi: 10.1016/j.jpsychires.2016.10.023. Epub 2016 Nov 22. No abstract available. PMID 27914292
• Results publication: Zarate CA Jr, Mathews D, Ibrahim L, Chaves JF, Marquardt C, Ukoh I, Jolkovsky L, Brutsche NE, Smith MA, Luckenbaugh DA. A randomized trial of a low-trapping nonselective N-methyl-D-aspartate channel blocker in major depression. Biol Psychiatry. 2013 Aug 15;74(4):257-64. doi: 10.1016/j.biopsych.2012.10.019. Epub 2012 Dec 1. PMID 23206319

• Carlos A Zarate, MD, Principal investigator, National Institute of Mental Health (NIMH)